SAR of beta blockers
The Structure-Activity Relationship (SAR) of beta blockers can be summarized based on the following key elements in their chemical structure:
1.Aryloxypropanolamine Structure:
Most beta blockers have this structure, which includes an aromatic ring, an ether oxygen, a 2-carbon spacer, and a secondary or tertiary amine.
2.Aromatic Ring:
An aromatic ring is crucial for beta-blocking activity. Different substituents on the ring can influence the lipophilicity and selectivity of the beta blocker.
3.Ether Linkage:
The ether oxygen connecting the aromatic ring to the rest of the molecule is essential for beta-blocking activity.
4.2-Carbon Spacer:
The two-carbon chain separating the ether oxygen and the amine is important for activity. Any changes in chain length can decrease the beta-blocking activity.
5.Amine:
The secondary or tertiary amine is also a key component. The S(-) enantiomer is usually more active than the R(+) enantiomer.
6.Substituents on the Nitrogen:
Any substituents on the nitrogen of the amine can influence the beta-blocking activity and selectivity. For instance, a selective β1 blocker like metoprolol has an isopropyl group on the nitrogen.
7.Additional Blocking Activity:
Some beta blockers, like labetalol, have additional alpha-blocking activity due to an additional phenyl ring on the amine.
Overall, alterations to these key structural components can influence not only the activity and selectivity of the beta blockers, but also their pharmacokinetic properties.